Abstract
Aberrant expression of miR-196a has been frequently reported in cancer studies. However, the expression and mechanism of its function in gastric cancer remains unclear. Quantitative real-time PCR was carried out to detect the relative expression of miR-196a in gastric cancer cell lines and tissues. SGC7901 cells were treated with miR-196a inhibitors, mimics, or pCDNA/miR-196a to investigate the role of miR-196a in cell proliferation. Higher expression of miR-196a in gastric cancer tissues was associated with tumor size, a higher clinical stage, and was also correlated with shorter overall survival of patients with gastric cancer. Exogenous downregulation of miR-196a expression significantly suppressed the in vitro cell-cycle progression, proliferation, and colony formation of gastric cancer cells, and ectopic miR-196a expression significantly enhanced the development of tumors in nude mice. Luciferase assays revealed that miR-196a inhibited p27(kip1) expression by targeting one binding site in the 3'-untranslated region (3'-UTR) of p27(kip1) mRNA. qPCR and Western blot assays verified that miR-196a reduced p27(kip1) expression at both mRNA and protein levels. The p27(kip1)-mediated repression in cell proliferation was reverted by exogenous miR-196a expression. A reverse correlation between miR-196a and p27(kip1) expression was noted in gastric cancer tissues. Our study shows that aberrant overexpression of miR-196a and consequent downregulation of p27(kip1) could contribute to gastric carcinogenesis and would be targets for gastric cancer therapies and further developed as potential prognostic factors.
Highlights
Gastric cancer is the second leading cause of cancer death and is the most common gastrointestinal malignancy in East Asia, Eastern Europe, and parts of Central and South America [1]
To validate levels of miR-196a expression, we conducted qRT-PCR analysis to measure the miR-196a expression in 36 gastric cancer tissues and 3 gastric cancer cell lines compared with normal counterparts
The results showed that expression of miR-196a was significantly upregulated in gastric cancer tissues and cells (Fig. 1A and B)
Summary
Gastric cancer is the second leading cause of cancer death and is the most common gastrointestinal malignancy in East Asia, Eastern Europe, and parts of Central and South America [1]. Malignant proliferation has been major reason for the dismal outcome of patients with gastric cancer. Increased cell proliferation is a common feature of gastric malignant proliferation. Gastrectomy remains the mainstay treatment of gastric cancer, but the prognosis for advanced stage patients is still very poor [2]. Authors' Affiliations: 1Department of Biochemistry and Molecular Biology, Departments of 2General Surgery and 3Oncology, First Affiliated Hospital, 4Department of Oncology, Second Affiliated Hospital, Nanjing Medical University, Nanjing, Jiangsu, PR China. Note: Supplementary material for this article is available at Molecular Cancer Therapeutics Online (http://mct.aacrjournals.org/).
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